Oxidative Stress, Inflammation, and Autophagic Stress as the Key Mechanisms of Premature Age-Related Hearing Loss in SAMP8 Mouse Cochlea
Oxidative Stress, Inflammation, and Autophagic Stress as the Key Mechanisms of Premature Age-Related Hearing Loss in SAMP8 Mouse Cochlea
复制标题
DOI：
10.1089/ars.2011.4037
复制
发表时间：
2012-02-01
影响因子：
6.6
通讯作者：
Wang, Jing
中科院分区：
文献类型：
--
作者：
Menardo, Julien;Tang, Yong;Wang, Jing
目的：在我们的老龄化社会中，年龄相关性听力损失（ARHL）或老年性耳聋越来越重要。在此，我们使用衰老加速型小鼠8（SAMP 8）来研究ARHL的机制，SAMP 8是一个有用的模型来探索衰老对生物学过程的影响。结果如下：我们发现SAMP 8菌株表现出过早的听力损失和耳蜗变性，重现了在人类老年性耳聋中观察到的过程（即，神经、感觉和神经变性）。与SAMP 8小鼠中过早ARHL相关的分子机制涉及氧化应激、抗氧化酶水平改变以及复合物I、II和IV活性降低，这反过来导致慢性炎症和触发凋亡细胞死亡途径。此外，螺旋神经节神经元（SGN）也经历自噬应激和积累脂褐素。创新与结论：我们的研究结果提供的证据表明，针对氧化应激，慢性炎症或凋亡途径可能具有治疗潜力。调节自噬可能是另一种策略。自噬应激和蛋白质聚集特异性地发生在SGN中的事实也为预防神经性老年性聋提供了有希望的前景。抗氧化剂。氧化还原信号。16，263-274.
Aims: In our aging society, age-related hearing loss (ARHL) or presbycusis is increasingly important. Here, we study the mechanism of ARHL using the senescence-accelerated mouse prone 8 (SAMP8) which is a useful model to probe the effects of aging on biological processes. Results: We found that the SAMP8 strain displays premature hearing loss and cochlear degeneration recapitulating the processes observed in human presbycusis (i.e., strial, sensory, and neural degeneration). The molecular mechanisms associated with premature ARHL in SAMP8 mice involve oxidative stress, altered levels of antioxidant enzymes, and decreased activity of Complexes I, II, and IV, which in turn lead to chronic inflammation and triggering of apoptotic cell death pathways. In addition, spiral ganglion neurons (SGNs) also undergo autophagic stress and accumulated lipofuscin. Innovation and Conclusion: Our results provide evidence that targeting oxidative stress, chronic inflammation, or apoptotic pathways may have therapeutic potential. Modulation of autophagy may be another strategy. The fact that autophagic stress and protein aggregation occurred specifically in SGNs also offers promising perspectives for the prevention of neural presbycusis. Antioxid. Redox Signal. 16, 263-274.